Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial

Prog Neuropsychopharmacol Biol Psychiatry. 2003 Sep;27(6):1007-12. doi: 10.1016/S0278-5846(03)00161-1.


The estrogen hypothesis of schizophrenia postulates that estrogen exerts a protective effect against schizophrenia and that this partly explains the observed sex differences in premorbid adjustment, onset age, treatment response, and illness course. It has been suggested that estrogen supplementation can augment the treatment effects of antipsychotics. The purpose of the present investigation was to access the efficacy of ethinyl estradiol as an adjuvant agent in the treatment of premenopausal women with chronic schizophrenia in an 8-week, double-blind, and placebo-controlled trial. Eligible participants in the study were 32 women of childbearing age with schizophrenia. All patients were inpatients, in the active phase of illness, and met DSM-IV criteria for chronic schizophrenia. Patients were allocated in a random fashion, 16 to haloperidol 15 mg/day plus ethinyl estradiol 0.05 mg/day and 16 to haloperidol 15 mg/day plus placebo for an 8-week, double-blind, placebo-controlled study. Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of haloperidol and ethinyl estradiol showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms as well as Positive and Negative Syndrome Scale (PANSS) total scores. Although the means Extrapyramidal Symptoms Rating Scale (ESRS) for the placebo group were higher than ethinyl estradiol group, the differences were not significant over the trial. A significant difference was observed between the overall mean biperiden dosages in the two groups. The results of this study suggest that estrogen may be an effective adjuvant agent in the management of women of childbearing age with chronic schizophrenia. Nevertheless, results of larger controlled trials are needed before recommendation for a broad clinical application can be made.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Chronic Disease
  • Double-Blind Method
  • Drug Therapy, Combination
  • Ethinyl Estradiol / therapeutic use*
  • Female
  • Haloperidol / therapeutic use*
  • Humans
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology


  • Ethinyl Estradiol
  • Haloperidol